17794-48-8Relevant articles and documents
Improvement of Oral Bioavailability of Pyrazolo-Pyridone Inhibitors of the Interaction of DCN1/2 and UBE2M
Kim, Ho Shin,Hammill, Jared T.,Scott, Daniel C.,Chen, Yizhe,Rice, Amy L.,Pistel, William,Singh, Bhuvanesh,Schulman, Brenda A.,Guy, R. Kiplin
supporting information, p. 5850 - 5862 (2021/05/29)
The cullin-RING ubiquitin ligases (CRLs) are ubiquitin E3 enzymes that play a key role in controlling proteasomal degradation and are activated by neddylation. We previously reported inhibitors that target CRL activation by disrupting the interaction of defective in cullin neddylation 1 (DCN1), a CRL neddylation co-E3, and UBE2M, a neddylation E2. Our first-generation inhibitors possessed poor oral bioavailability and fairly rapid clearance that hindered the study of acute inhibition of DCN-controlled CRL activity in vivo. Herein, we report studies to improve the pharmacokinetic performance of the pyrazolo-pyridone inhibitors. The current best inhibitor, 40, inhibits the interaction of DCN1 and UBE2M, blocks NEDD8 transfer in biochemical assays, thermally stabilizes cellular DCN1, and inhibits anchorage-independent growth in a DCN1 amplified squamous cell carcinoma cell line. Additionally, we demonstrate that a single oral 50 mg/kg dose sustains plasma exposures above the biochemical IC90 for 24 h in mice.
Piperidine thiazole derivative containing bisamide structure as well as preparation method and application thereof
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Paragraph 0021, (2019/02/03)
The invention discloses a piperidine thiazole derivative containing a bisamide structure, and also discloses a preparation method of the piperidine thiazole derivative and application of the piperidine thiazole derivative as a sterilization agent and an insecticide. The invention provides the novel piperidine thiazole derivative containing the bisamide structure; the preparation method is simpleand convenient; the piperidine thiazole derivative can be used for preventing and treating cucumber gray mold, rice sheath blight diseases and potato late blight diseases, has good sterilization activity, can be used for preventing and treating insect pest of armyworm, black bean aphid, tetranychus telarius linne and the like, and lays the foundation for the invention and development of piperidinethiazole pesticides.
PIPERAZINYL 3-AMINOPYRROLIDINE DERIVATIVES AS A CCR2 ANTAGONIST
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Page/Page column 17, (2012/06/01)
The present invention relates to compounds of chemical formula I and having CCR2 (chemokine receptor 2) antagonistic effects, and salts or isomers thereof. These compounds are very useful for treating, preventing, or relieving rheumatoid arthritis, arteri
PIPERAZINYL 3-AMINOPYRROLIDINE DERIVATIVES AS A CCR2 ANTAGONIST
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Page/Page column 11-12, (2012/07/31)
The present invention relates to compounds of chemical formula 1 and having CCR2 (chemokine receptor 2) antagonistic effects, and salts or isomers thereof. These compounds are very useful for treating, preventing, or relieving rheumatoid arthritis, arteri
A METHOD OF TREATING LIVER FIBROSIS
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Page/Page column 36, (2012/09/11)
The present invention relates to a method of treating hepatis C and/or liver fibroisis with 3-cycloalkylaminopyrrolidine derivatives of the present invention
4-AZETIDINYL-1-HETEROARYL-CYCLOHEXANOL ANTAGONISTS OF CCR2
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Page/Page column 61-62, (2010/06/19)
The present invention comprises compounds of Formula (I). wherein: R1, R2, R3, and R4 are as defined in the specification. The invention also comprises pharmaceutical compositions comprising the compounds of formula (I) and methods of preventing, treating or ameliorating a CCR2 mediated syndrome, disorder or disease, for example, type II diabetes, obesity or asthma, by administering the compounds of formula (I).
Synthesis and biological evaluation of 3-aminopyrrolidine derivatives as CC chemokine receptor 2 antagonists
Lim, Jee Woong,Oh, Youna,Kim, Jong-Hoon,Oak, Min-Ho,Na, Yongho,Lee, Jung-Ok,Lee, Seung-Woo,Cho, Heeyeong,Park, Woo-Kyu,Choi, Gildon,Kang, Jongmin
scheme or table, p. 2099 - 2102 (2010/07/06)
Novel 3-aminopyrrolidine derivatives were synthesized and evaluated for their antagonistic activity against human chemokine receptor 2. Structure-activity studies on 3-aminopyrrolidine incorporating heteroatomic carbocycle moieties led to piperidine compo
Discovery of INCB3344, a potent, selective and orally bioavailable antagonist of human and murine CCR2
Xue, Chu-Biao,Wang, Anlai,Meloni, David,Zhang, Ke,Kong, Ling,Feng, Hao,Glenn, Joseph,Huang, Taisheng,Zhang, Yingxin,Cao, Ganfeng,Anand, Rajan,Zheng, Changsheng,Xia, Michael,Han, Qi,Robinson,Storace, Lou,Shao, Lixin,Li, Mei,Brodmerkel, Carrie M.,Covington, Maryanne,Scherle, Peggy,Diamond, Sharon,Yeleswaram, Swamy,Vaddi, Kris,Newton, Robert,Hollis, Greg,Friedman, Steven,Metcalf, Brian
body text, p. 7473 - 7478 (2011/01/12)
Rational design based on a pharmacophore of CCR2 antagonists reported in the literature identified lead compound 9a with potent inhibitory activity against human CCR2 (hCCR2) but moderate activity against murine CCR2 (mCCR2). Modification on 9a led to the
3-Cycloalkylaminopyrrolidine derivatives as modulators of chemokine receptors
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Page/Page column 21, (2008/06/13)
The present invention relates to 3-cycloalkylaminopyrrolidine derivatives of the formula I: (wherein R1, R2, R3, R4, R5, R6, R7, X, Y and Z are as defined herein) which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of chemokine receptors and more specifically as modulators of the CCR2 and/or CCR5 receptor. The compounds and compositions of the invention may bind to chemokine receptors, e.g., the CCR2 and/or CCR5 chemokine receptors, and are useful for treating diseases associated with chemokine, e.g., CCR2 and/or CCR5, activity, such as atherosclerosis, restenosis, lupus, organ transplant rejection and rheumatoid arthritis.
Anthranilate 4H-oxazol-5-ones: Novel small molecule antibacterial acyl carrier protein synthase (AcpS) inhibitors
Gilbert, Adam M.,Kirisits, Matthew,Toy, Patrick,Nunn, David S.,Failli, Amadeo,Dushin, Elizabeth G.,Novikova, Elena,Petersen, Peter J.,Joseph-Mccarthy, Diane,McFadyen, Iain,Fritz, Christian C.
, p. 37 - 41 (2007/10/03)
D-optimal design and Projection to Latent Structures (PLS) analysis were used to optimize screening hit 5 (B. subtilis AcpS IC50: 15 μM, B. subtilis MIC: >200 μM) into a series of 4H-oxazol-5-one, small molecule, antibacterial, AcpS inhibitors. Specifically, 15, 16 and 18 show μM or sub-μM AcpS inhibition (IC50s: 15: 1.1 μM, 16: 1.5 μM, 18: 0.27 μM) and moderate antibacterial activity (MICs: 12.5-50 μM) against B. subtilis, E. faecalis ATCC, E. faecalis VRE and S. pneumo+.
